Preparation of microparticles having a selected release profile

Abstract

An improved method for preparing microparticles that exhibit controlled release of an effective amount of an active agent over an extended period of time. More particularly, a method is provided for preparing microparticles having a selected release profile for release of active agent contained in the microparticles. By adjusting the degree of drying that is performed during the preparation of the microparticles, the release profile can be controlled. By performing no intermediate drying, an initial burst and a substantially linear release profile is achieved. By performing substantially complete intermediate drying, an initial lag phase and a substantially sigmoidal release profile is achieved.

What is claimed is:  
     
       1. A method for preparing microparticles having a selected release profile for release of active agent contained in the microparticles, comprising: 
       (a) preparing an emulsion that comprises a first phase and a second phase, wherein the first phase comprises the active agent, a polymer, and a solvent for the polymer;  
       (b) extracting at least a portion of the solvent from the emulsion to form microparticles containing the active agent;  
       (c) selecting a degree of intermediate drying of the microparticles to be performed so that the selected release profile is achieved; and  
       (d) final drying the microparticles.  
     
     
       2. The method of  claim 1 , wherein the selecting step (c) is carried out to select no intermediate drying, thereby resulting in microparticles having an initial burst and a substantially linear release profile. 
     
     
       3. The method of  claim 1 , wherein the selecting step (c) is carried out to select substantially complete intermediate drying, thereby resulting in microparticles having an initial lag phase and a substantially sigmoidal release profile. 
     
     
       4. The method of  claim 3 , further comprising after step (c): 
       (e) performing the selected degree of intermediate drying.  
     
     
       5. The method of  claim 4 , wherein the substantially complete intermediate drying results in the microparticles having a moisture content of less than about 0.2% after step (e). 
     
     
       6. The method of  claim 1 , further comprising after step (c): 
       (e) washing the microparticles.  
     
     
       7. The method of  claim 1 , wherein extracting step (b) is carried out using a quench liquid. 
     
     
       8. A method for controlling a release profile of an active agent contained in microparticles, comprising: 
       (a) forming microparticles containing the active agent;  
       (b) selecting a degree of drying of the microparticles to be performed, wherein the degree of drying affects the release profile of the active agent from the microparticles; and  
       (c) performing the selected degree of drying.  
     
     
       9. The method of  claim 8 , wherein the selecting step (b) is carried out to select final drying and no intermediate drying, thereby resulting in an initial burst of the active agent and a substantially linear release of the active agent. 
     
     
       10. The method of  claim 8 , wherein the selecting step (b) is carried out to select final drying and substantially complete intermediate drying, thereby resulting in an initial lag in release of the active agent, and a substantially sigmoidal release of the active agent. 
     
     
       11. A microencapsulated active agent having a selected release profile prepared by a method for preparing microparticles, the method comprising: 
       (a) preparing an emulsion that comprises a first phase and a second phase, wherein the first phase comprises the active agent, a polymer, and a solvent for the polymer;  
       (b) extracting at least a portion of the solvent from the emulsion to form microparticles containing the active agent;  
       (c) selecting a degree of intermediate drying of the microparticles to be performed so that the selected release profile is achieved; and  
       (d) final drying the microparticles.  
     
     
       12. The microencapsulated active agent of  claim 11 , wherein the selecting step (c) is carried out to select no intermediate drying, thereby resulting in microparticles having an initial burst and a substantially linear release profile. 
     
     
       13. The microencapsulated active agent of  claim 11 , wherein the selecting step (c) is carried out to select substantially complete intermediate drying, thereby resulting in microparticles having an initial lag phase and a substantially sigmoidal release profile. 
     
     
       14. The microencapsulated active agent of  claim 11 , wherein the method further comprises after step (c): 
       (e) performing the selected degree of intermediate drying.  
     
     
       15. The microencapsulated active agent of  claim 14 , wherein the substantially complete intermediate drying results in the microparticles having a moisture content of less than about 0.2% after step (e). 
     
     
       16. Microparticles prepared by the method of  claim 1 . 
     
     
       17. Microparticles prepared by the method of  claim 3 . 
     
     
       18. Microparticles prepared by the method of  claim 7 .